Pharmaceutical compositions and methods for managing skin conditions

ABSTRACT

This application relates to a pharmaceutical composition and methods for treating inflammatory skin conditions. The compositions include hydrogen peroxide, one or more moisturizing agents, and an anti-inflammatory agent. The pharmaceutical compositions may optionally include one or more exfoliants. The compositions can be used to treat inflammatory skin conditions such as dermatitis, including, but not limited to seborrheic dermatitis, nummular dermatitis, contact dermatitis, atopic dermatitis, exfoliative dermatitis, perioral dermatitis, and stasis dermatitis; psoriasis; folliculitis; rosacea; acne; impetigo; erysipelas; paronychia, erythrasma; and eczema.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of application Ser.No. 09/878,231, filed Jun. 12, 2001, currently pending, of which is acontinuation of application Ser. No. 09/549,202, filed Apr. 13, 2000,now allowed, which is a continuation-in-part of application Ser. No.09/330,127, filed Jun. 11, 1999, currently U.S. Pat. No. 6,071,541,which is a continuation-in-part of provisional Application No.60/094,775, filed Jul. 31, 1998.

TECHNICAL FIELD

[0002] This application relates to pharmaceutical compositions andmethods to cleanse skin and facilitate the prevention, treatment, andmanagement of skin conditions.

BACKGROUND OF THE INVENTION

[0003] Human skin is a composite material of the epidermis and thedermis. The topmost part of the epidermis is the stratum corneum. Thislayer is the stiffest layer of the skin, as well as the one mostaffected by the surrounding environment. Below the stratum corneum isthe internal portion of the epidermis. Below the epidermis, the topmostlayer of the dermis is the papillary dermis, which is made of relativelyloose connective tissues that define the micro-relief of the skin. Thereticular dermis, disposed beneath the papillary dermis, is tight,connective tissue that is spatially organized. The reticular dermis isalso associated with coarse wrinkles. At the bottom of the dermis liesthe subcutaneous layer.

[0004] The principal functions of the skin include protection,excretion, secretion, absorption, thermoregulation, pigmentogenesis,accumulation, sensory perception, and regulation of immunologicalprocesses. These functions are detrimentally affected by; for example,dryness, yeast, and structural changes in the skin, such as due to agingand excessive sun exposure. Various pharmaceuticals have been used forthe treatment or prevention of skin conditions, including skin cleansingcompositions. Some of these compositions are discussed below.

[0005] Canadian Patent No. 1,174,976 discloses a germ-killing skinmedication including two gels to be applied and mixed in situ, the firstgel having sodium chlorite in an aqueous form and the second gel havinglactic acid in an aqueous gel.

[0006] Great Britain Application No. 2,076,286 A discloses adermatological composition of an oil medium dispersed in an aqueousmedium that contains hydrogen peroxide, a buffer to maintain thecomposition below a pH of 7, and a starch gelled in situ. The buffer mayinclude lactic, citric, tartaric, maleic, or hydroxysuccinic acids withan acid salt.

[0007] Great Britain Application No. 2,189,394 A discloses a concentratethat can be mixed with hydrogen peroxide to become an effectivedisinfectant for water, foodstuff, animal feeds, equipment, packages,and the like. The concentrate includes an inorganic acid with a pH lessthan 1.6, a silver compound or colloidal silver, an organic acidstabilizer such as tartaric, lactic, salicylic, or citric acid, andoptionally gelatin.

[0008] European Patent Application No. 0,191,214 A2 discloses a cosmeticliquid cleanser for treating blemished, scarred, or inflamed skin havingboric acid or borax, ammonium hydroxide, a peroxide, and optionallysalicylic acid.

[0009] European Patent No. 0,250,539 B1 discloses a stabilized aqueoushydrogen peroxide composition having 0.1 to 4 weight percent hydrogenperoxide and 0.5 to 5 weight percent β-crystals of one or more lipidsselected from monoglycerides of fatty acids, ascorbic acid, phosphate orlactic acid esters of fatty acids and monoglycerol ethers, said fattyacids and ether chains being saturated and having 12 to 18 carbons.

[0010] European Patent No. 0,425,507 B1 discloses compositions fortreating abnormal or damaged conditions of the epithelium includingskin, which include 0.01 to 12 weight percent of an activated proteincontaining at least 0.5 weight percent cysteine, 0.1 to 15 weightpercent of a reducing agent to reduce cystine to cysteine, and 81.0 to99.889 weight percent water, acids, bases, buffering agents, emulsifyingagents, thickeners, solvents, preservatives, coloring agents, andperfuming agents. The reducing agent may be a salt of a thioglycolicacid. In a preferred embodiment, the composition also includes anoxidizing agent, such as hydrogen peroxide.

[0011] U.S. Pat. No. 3,297,456 discloses cleaning and polishingcompositions, particularly for floor waxing, having lactic acid,methanol, hydrogen peroxide, and aqua ammonia in a particular ratio.

[0012] U.S. Pat. Nos. 4,051,058 and 4,051,059 disclose stableperoxy-containing concentrates useful for the production of microbicidalagents consisting essentially of an aqueous mixture of 0.5 to 20 weightpercent peracetic or perpropionic acid or their precursors, 25 to 40weight percent hydrogen peroxide, and optionally up to 5 weight percentanionic surface-active compounds of the sulfonate and sulfate type. Alsodisclosed are compositions that further include 0.25 to 10 weightpercent organic phosphonic acid capable of sequestering bivalent metalcations and their water-soluble acid salts.

[0013] U.S. Pat. No. 4,203,765 discloses an aqueous acidic etch-bleachsolution of hydrogen peroxide, iron ions, and inorganic anions that forma silver salt, such that in the dissolved state the solution containscitric acid and a polymer of alkylene oxide units for stabilization ofthe hydrogen peroxide.

[0014] U.S. Pat. No. 4,438,102 discloses compositions containinggelatin, hydrogen peroxide, ammonium hydroxide, thioglycolic acid, and alower alkanol to promote the growth of dermal and epidermal tissue.

[0015] U.S. Pat. No. 4,534,945 discloses an aqueous 25 to 35 weightpercent solution of hydrogen peroxide stabilized against decompositionwith up to 1.4 mg/L tin, which is maintained in solution by particularamounts of phosphate in the form of phosphonic acid andhydroxycarboxylic acid.

[0016] U.S. Pat. No. 4,557,935 discloses a germicidal composition ofhydrophilic lipid crystals of 1-monolaurin, and preferably1-monomyristin, and hydrogen peroxide, whereby the former stabilize thelatter. Optionally, the compositions further contain salicylic acid.

[0017] U.S. Pat. No. 4,900,721 discloses liquid, aqueous disinfectantsbased on alcohol and hydrogen peroxide that contain one or more C₂₋₈alcohols, hydrogen peroxide or a hydrogen peroxide forming compound, oneor more carboxylic acids, one or more microbicidally activenitrogen-containing organic compounds, one or more microbicidally activephenolic compounds for disinfection of the skin and mucous membrane.

[0018] U.S. Pat. No. 5,139,788 discloses an antimicrobial surfacesanitizing composition having a diluent and antimicrobial agent of anantimicrobially effective amount of alpha-hydroxyacid substituted mono-or di-carboxylic acid and an antimicrobially effective amount ofhydrogen peroxide, such that the composition leaves a non-contaminatingresidue after contact with surfaces to be disinfected.

[0019] U.S. Pat. No. 5,693,318 discloses phosphate esters for theimprovement of water solubility of salicylic acid and peroxide compoundsin an aqueous cleanser.

[0020] Despite these references, there remains a need for improvedpharmaceutical compositions and methods of treating inflammatory skinconditions.

SUMMARY OF THE INVENTION

[0021] The present invention relates to a topical anti-inflammatorypharmaceutical composition that includes hydrogen peroxide in an amountsufficient to cleanse the skin; a moisturizing agent in an amountsufficient to facilitates hydration of the skin; and ananti-inflammatory agent to in an amount sufficient to reduceinflammation of the skin. The hydrogen peroxide is present in an amountfrom about 0.01 to 6 weight percent by weight of the composition, themoisturizing agent is present in an amount of about 0.01 to 20 weightpercent by weight of the composition, and the anti-inflammatory agent ispresent in an amount of about 0.02 to 2 weight percent by weight of thecomposition.

[0022] The moisturizing agent can be a hydrophobic moisturizing agentsuch as ceramide, borage oil, tocopherol, tocopherol linoleate,dimethicone, glycerine, or a mixture thereof or a hydrophilicmoisturizing agent such as hyaluronic acid, sodium peroxylinecarbolicacid, wheat protein, hair keratin amino acids, or a mixture thereof.

[0023] The pharmaceutical composition can further include apharmaceutically acceptable carrier or excipient. The pharmaceuticalcomposition can be a gel, paste, cream, lotion, emulsion, or ointment.

[0024] The pharmaceutical composition may further include an exfoliant.The exfoliant can be an enzymatic exfoliant or a mono- or -poly-hydroxyacid such as alpha-hydroxy acid, beta-hydroxy acid, or tannic acid. Inone embodiment the exfoliant is glycolic acid, lactic acid, citric acid,salicylic acid, or tannic acid.

[0025] The pharmaceutical composition may also include an amount ofamphoteric surfactant and an amount of citric acid sufficient to inhibithydrogen peroxide decomposition for at least three months, preferablyfor 3 months at 40° C. The pharmaceutical composition may also includeat least one of a surfactant, a stabilizer, a preservative, ananti-oxidant, or a coloring agent, which together may be present in anamount from about 10.1 to 99.1 weight percent of the composition.

[0026] The invention also relates to a method of managing aninflammatory skin condition which comprises topically administering to apatient a therapeutically effective amount of hydrogen peroxide in anamount sufficient to cleanse the skin; a moisturizing agent in an amountsufficient to facilitates hydration of the skin; and ananti-inflammatory agent to in an amount sufficient to reduceinflammation of the skin. The skin condition can be dermatitis,psoriasis, folliculitis, rosacea, acne, impetigo, erysipelas,paronychia, erythrasma, and eczema. The amount of the hydrogen peroxide,moisturizing agent, and anti-inflammatory agent administered is about 1mg to 20,000 mg per day.

[0027] The method can further involve administering one or more seconddermatological agents selected from a moisturizer, anti-inflammatoryagent, analgesic, or anesthetic by a route other than topicaladministration. The one or more second dermatological agents can be amoisturizer selected from panthenol, primrose oil, omega-3 fish oils,omega-6 fish oils, linoleic acid, flax seed oil, and mixtures thereof.The one or more second dermatological agents can be an anti-inflammatoryagent selected from aspirin, ibuprofen, ketoprofen, naproxen, andmixtures thereof.

[0028] The method can also include administering one or more exfoliantsin an amount sufficient to exfoliate at least a portion of the skin. Theexfoliant can be an enzymatic exfoliant or a mono- or -poly-hydroxyacid. In one embodiment the exfoliant an alpha-hydroxy acid,beta-hydroxy acid, or tannic acid. In another embodiment the exfoliantis glycolic acid, lactic acid, citric acid, salicylic acid, or tannicacid.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0029] The present invention is directed to a pharmaceutical compositionfor the prevention, treatment, and management of inflammatory skinconditions. The management of inflammatory skin conditions canadvantageously be accomplished by the administration of thepharmaceutical compositions of the present invention. Accordingly,methods for administering the compositions for management of aninflammatory skin condition are also encompassed by the invention. Themethods are used for the prevention, treatment, or management of one ormore inflammatory skin conditions.

[0030] The term “inflammatory skin conditions,” as used herein, meansconditions present any where on the skin that causes inflammation, i.e.,reddening, pain, or swelling of the skin and which may be accompanied bya rash, sores, blisters or other skin eruptions. Examples ofinflammatory skin conditions include, but are not limited to,dermatitis, including, but not limited to seborrheic dermatitis,nummular dermatitis, contact dermatitis, atopic dermatitis, exfoliativedermatitis, perioral dermatitis, and stasis dermatitis; psoriasis;folliculitis; rosacea; acne; impetigo; erysipelas; paronychia,erythrasma; eczema; and the like.

[0031] The terms “managing” or “management,” as used herein, includesone or more of the prevention, treatment, or modification of a skincondition.

[0032] The hydrogen peroxide is present in an amount sufficient tocleanse at least a portion of the skin. “Cleanse” as used hereinincludes the removal of dirt, debris, air pollutants, desquamatingcells, and cutaneous secretions of the skin. Preferably, the hydrogenperoxide is present in an amount to cleanse the skin without substantialirritation. The hydrogen peroxide is typically present in an amount fromabout 0.01 to 6 weight percent, preferably 0.05 to 4 weight percent, andmore preferably 0.1 to 1 weight percent of the composition. Withoutwishing to be bound by theory it is believed that cleansing the skinwith hydrogen peroxide improves penetration of the anti-inflammatoryinto the skin.

[0033] The pharmaceutical compositions include one or more moisturizingagents. “Moisturizing agent,” as used herein, is used to include anyagent that facilitates hydration of the skin by inhibiting or preventingloss of water from the skin, absorbs water from the atmosphere andhydrates the skin, or enhances the skin's own ability to absorb waterdirectly from the atmosphere, or a combination thereof. Without wishingto be bound by theory it is believed that the moisturizing agent alsoimproves the skins ability to absorb the anti-inflammatory agent.Furthermore, moisturizing agents also minimize- or prevent the skin fromdrying and cracking; cracked skin is more susceptible to environmentalfactors that generate free radicals, which are believed to cause furtherdamage to the skin. Suitable moisturizing agents include, but are notlimited to, hydrophobic agents, and hydrophilic agents, or combinationsthereof. Moisturizers, when used, are typically present in an amountfrom about 0.01 to 20 weight percent, preferably about 0.05 to 10 weightpercent, more preferably from about 0.1 to 5 weight percent of thecomposition.

[0034] Moisturizing agents that are hydrophobic agents include, but arenot limited to, ceramide, borage oil (linoleic acid), tocopherol(Vitamin E), tocopherol linoleate, dimethicone, glycerine, and mixturesthereof. Hydrophobic agents, when present, are believed to moisturizethe skin by inhibiting or preventing the loss of water from the skin.The hydrophobic agent, when present, is typically present in an amountfrom about 0.01 to weight percent, preferably from about 0.05 to 15weight percent, and more preferably from about 0.1 to 5 weight percentof the composition.

[0035] Moisturizing agents that are hydrophilic agents include, but arenot limited to, hyaluronic acid, sodium peroxylinecarbolic acid (sodiumPCA), wheat protein (e.g., laurdimonium hydroxypropyl hydrolyzed wheatprotein), hair keratin amino acids, and mixtures thereof. Sodiumchloride may also be present, particularly when hair keratin amino acidsare included as a moisturizer. Hydrophilic agents, when present, arebelieved to moisturize the skin by absorbing moisture from theatmosphere to hydrate or facilitate hydration of the skin. Thehydrophilic agent, when present, is typically present in an amount fromabout 0.01 to 20 weight 2 percent, preferably from about 0.05 to 15weight percent, and more preferably from about 0.1 to 5 weight percentof the composition.

[0036] Other moisturizing agents that hydrate the skin and are useful inthe compositions and methods of the present invention include, butte notlimited to, panthenol; primrose oil; GLA 3 and other fish oils that mayinclude, for example, the omega-3 and omega-6 oils and/or linoleic acid;and flax seed oil. Preferably, these moisturizing agents areadministered orally.

[0037] The compositions and methods for managing inflammatory skinconditions also include one or more anti-inflammatory agents in anamount sufficient to reduce inflammation of the skin. In one embodimentthe anti-inflammatory agent is a steroidal anti-inflammatory. Suitablesteroidal anti-inflammatory agents for use in the compositions andmethods of the invention include the corticosteroids such as, but notlimited to, hydrocortisone, fluocinolone acetonide, halcinonide,halobetasol propionate, clobetasol propionate, betamethasonedipropionate, betamethasone valerate, and triamcinolone acetonide.

[0038] In another embodiment the anti-inflammatory agent is anon-steroidal anti-inflammatory agent. Examples of suitablenon-steroidal anti-inflammatory agents for use in the compositions andmethods of the invention include, but are not limited to, aspirin,ibuprofen, ketoprofen, and naproxen. These anti-inflammatory agents arepreferably administered orally. Other non-steroidal anti-inflammatoryagents useful in the compositions of the invention include, but are notlimited to aloe vera gel, aloe vera, licorice extract, pilewort,Canadian willow root, and zinc, and allantoin. Allantoin is a preferrednon-steroidal anti-inflammatory agent. The anti-inflammatory agents areused in an amount sufficient to inhibit or reduce inflammation,preferably in an amount from about 0.02 to 2 weight percent, preferablyfrom about 0.1 to 1.5 weight percent, and more preferably from about 0.2to 1 weight percent of the composition. It should be understood, withreference to managing skin conditions, that the anti-inflammatory agentsfacilitate inhibition or suppression of inflammation any where on theskin. Arnica Montana (a healing herb) and vitamin K can also be used asthe anti-inflammatory. Arnica Montana facilitates skin healing and actsas an antiseptic and local anti-inflammatory, and, when used, istypically present in an amount from about 0.1 to 2 weight percent,preferably about 0.2 to 1 weight percent. The Vitamin K inhibits orsuppresses inflammation and bruising (i.e., acts as an anti-inflammatoryand anti-bruising agent) and, when used, is typically present in anamount from about 0.01 to 1 weight percent, preferably from about 0.1 to0.5 weight percent.

[0039] Without wishing to be bound by theory it is believed that thecomponents of the invention interact in a synergistic manner to providethe desired management of the skin. Together, the hydrogen peroxide,moisturizing agent, and anti-inflammatory agent cleanse the skin, removesubstances foreign to the skin, and moisturize the skin to improvepenetration of the anti-inflammatory agent to inhibit or reduceinflammation of the skin and generally facilitate management ofinflammatory skin conditions. In particular, the compositions of theinvention reduce or eliminate the redness, swelling, sores, and blisterstypically associated with inflammatory skin conditions. The synergisticeffect provides a composition for treating inflammatory skin conditionsthat is superior to using the anti-inflammatory alone.

[0040] In a preferred embodiment, the dermatological agent furtherincludes an exfoliant to help remove dead or dying skin cells andfurther improve the skin's own ability to absorb moisture directly fromthe atmosphere in combination with one or more hydrophilic agents tohelp absorb moisture from the atmosphere and hydrate the skin or incombination with one or more a hydrophobic agents to inhibit or preventmoisture loss by the skin. More preferably, the pharmaceuticalcomposition includes one or more of a hydrophilic agent and one or moreof a hydrophobic agent in combination with an exfoliant. It is alsobelieved that the exfoliant also helps the anti-inflammatory componentpenetrate the skin.

[0041] The exfoliant may be an enzymatic exfoliant, or an acidicexfoliant. Any enzymatic exfoliant known to those skilled in the art maybe used in the compositions and methods of the invention. Examples ofenzymatic exfoliants useful in the compositions and methods of theinvention include, but are not limited to, papain, from papaya, andbromalein, from pineapple.

[0042] Examples of acidic exfoliants include, but are not limited to amono- or poly-hydroxy acid, tannic acid, or a mixture thereof, or apharmaceutically acceptable salt or ester thereof. One of ordinary skillin the art will be readily able to select and prepare suitable mono- orpoly-hydroxy acids for use in the composition of the invention, forexample, alkyl hydroxycarboxylic acids, aralkyl and arylhydroxycarboxylic acids, polyhydroxy-carboxylic acids, andhydroxy-polycarboxylic acids. One of ordinary skill in the art wouldtypically select one or more of the following mono- or poly-hydroxyacids: 2-hydroxyacetic acid (glycolic acid); 2-hydroxypropanoic acid(lactic acid); 2-methyl 2-hydroxypropanoic acid; 2-hydroxybutanoic acid;phenyl 2-hydroxyacetic acid; phenyl 2-methyl 2-hydroxyacetic acid;3-phenyl 2-hydroxyacetic acid; 2,3-dihydroxypropanoic acid;2,3,4-trihydroxybutanoic acid; 2,3,4,5,6-pentahydroxyhexanoic acid;2-hydroxydodecanoic acid; 2,3,4,5-tetrahydroxypentanoic acid;2,3,4,5,6,7-hexahydroxyheptanoic acid; diphenyl 2-hydroxyacetic acid;4-hydroxymandelic acid; 4-chloromandelic acid; 3-hydroxybutanoic acid;4-hydroxybutanoic acid; 2-hydroxyhexanoic acid; 5-hydroxydodecanoicacid; 12-hydroxydodecanoic acid; 10-hydroxydecanoic acid;16-hydroxyhexadecanoic acid; 2-hydroxy-3-methylbutanoic acid;2-hydroxy-4-methylpentanoic acid; 3-hydroxy-4-methoxymandelic acid;4-hydroxy-3-methoxymandelic acid; 2-hydroxy-2-methylbutanoic acid;3-(2-hydroxyphenyl) lactic acid; 3-(4-hydroxyphenyl) lactic acid;hexahydromandelic acid; 39 hydroxy-3-methylpentanoic acid;4-hydroxydecanoic acid; 5-hydroxydecanoic acid; aleuritic acid;2-hydroxypropanedioic acid; 2-hydroxybutanedioic acid; erythraric acid;threaric acid; arabiraric acid; ribaric acid; xylaric acid; lyxaricacid; glucaric acid; galactaric acid; mannaric acid; gularic acid;allaric acid; altraric acid; idaric acid; talaric acid;2-hydroxy-2-methylbutanedioic acid; citric acid, isocitric acid,agaricic acid, quinic acid, glucoronic acid, glucoronolactone,galactoronic acid, galactoronolactone, uronic acids, uronolactones,ascorbic acid, dihydroascorbic acid, dihydroxytartaric acid, tropicacid, ribonolactone, gluconolactone, galactonolactone, gulonolactone,mannonolactone, citramalic acid; pyruvic acid, hydroxypyruvic acid,hydroxypyruvic acid phosphate and esters thereof; methylpyruvate, ethylpyruvate, propyl pyruvate, isopropyl pyruvate; phenyl pyruvic acid andesters thereof; methyl phenyl pyruvate, ethyl phenyl pyruvate, propylphenyl pyruvate; formyl formic acid and esters thereof; methyl formylformate, ethyl formyl formate, propyl formyl formate; benzoyl formicacid and esters thereof; methyl benzoyl formate, ethyl benzoyl formateand propyl benzoyl formate; 4-hydroxybenzoyl formic acid and estersthereof; 4-hydroxyphenyl pyruvic acid and esters thereof; and2-hydroxyphenyl pyruvic acid and esters thereof.

[0043] In one embodiment the poly-hydroxy acidic components is analpha-hydroxy acid. Preferred alpha-hydroxy acids include citric acid,glycolic acid, lactic acid. In another embodiment the poly-hydroxyacidic exfoliant is a beta-hydroxy acid. A preferred beta-hydroxy acidis salicylic acid.

[0044] The term “pharmaceutically acceptable salt” refers to a saltprepared from pharmaceutically acceptable non-toxic acid. Examples ofsuitable inorganic metallic bases for salts formation with the acidcompounds of the invention include, but are not limited to, aluminum,calcium, lithium, magnesium, potassium, sodium, and zinc. Appropriateorganic bases may be selected, for example, fromN,N-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine,ethylenediamine, meglumaine (N-methylglucamine), and procaine.

[0045] It should be understood that one or more derivatives of the aboveacidic component, such as esters or lactones thereof, are also suitablyused. One of ordinary skill in the art will also understand that varioushydroxy acids described in U.S. Pat. Nos. 5,547,988 and 5,422,370 arealso suitable for use in the compositions and methods of the invention.The acidic component is present in the composition and methods in anamount sufficient to exfoliate, i.e., remove dead or dying skin cells,from at least a portion of the skin. The acidic component is typicallypresent in an amount from about 0.1 to 12 weight percent, preferablyabout 1 to 11 weight percent, more preferably from about 4 to 10 weightpercent of the composition. For example, the acidic component may befrom about 0.1 to 3 weight percent citric acid in combination with up toabout 2 weight percent salicylic acid.

[0046] In another embodiment, the pharmaceutical compositions furthercomprise a pharmaceutically acceptable antimicrobial agent. Anypharmaceutically acceptable antimicrobial agent available to those ofordinary skill in the art may be used, but preferably at least one of anantibacterial agent, antifungal agent, antiviral agent, or anthelminticwill be used according to the invention. A single broad spectrumantimicrobial agent, i.e., one that is believed to have at least two ofantibacterial, antifungal, and antiviral efficacy, include: echinacea,golden seal, benzalkonium chloride, benzethonium chloride, iodine, grapeseed extract, pomegranate extract, green tea extract or polyphenols, andthe like, or combinations thereof, may be included. Another suitableantimicrobial agent includes the class of anthelmintics, such asmetronidazole, to facilitate treatment of, e.g., tricomona infection.Preferred antiviral agents include, but are not limited to, acyclovir,tamvir, penciclovir, and the like, and mixtures thereof. Preferredantibacterial agents include, but are not limited to, triclosan,neomycin, polymyxin, bacitracin, clindamycin, benzoyl peroxide, atetracycline, a sulfa drug, a penicillin, a quinolone, a cephalosporin,and mixtures thereof. Preferred antifungal agents include, but are notlimited to, farnesol, econazole, fluconazole, clotrimazole,ketoconazole, calcium or zinc undecylenate, undecylenic acid, butenafinehydrochloride, ciclopirox olaimine, miconazole nitrate, nystatin,sulconazole, terbinafine hydrochloride, and the like, and mixturesthereof. Exemplary tetracyclines include doxycycline and minocycline. Anexemplary sulfa drug includes sulfacetamde. An exemplary cephalosporinincludes cephalexin (commercially available as KEFLEX). Exemplaryquinolones include the floxacins, such as loemfloxacin, ofloxacin, andtrovafloxacin. It should be readily understood that any salts, isomers,pro-drugs, metabolites, or other derivatives of these antimicrobialagents may also be included as the antimicrobial agent in accordancewith the invention. The antimicrobial agent is typically present in anamount from about 0.01 to 1.5 weight percent, preferably from about 0.1to 1.2 weight percent, and more preferably from about 0.3 to 1 weightpercent of the composition. The antimicrobial agent inhibits theformation, and may further reduce, the presence of microbes that causeredness, inflammation, and irritation of the skin.

[0047] In another embodiment, the compositions further include one ormore of a vitamin A source including retinyl palmitate or other retinylesters, retinoic acid, or Retinol. The Retinol facilitates normal skinproduction, particularly epidermal normalization, and, when used, istypically present in an amount from about 0.01 to 6 weight percent,preferably about 0.1 to 5 weight percent.

[0048] The compositions of the invention may further include one or moresurfactants, stabilizers, preservatives, coloring agents, anti-oxidants,water, buffering agents, emulsifying agents, thickeners, solvents,perfuming agents, and the like. Preferably, the water is deionizedwater. It should be understood that water includes the remainder of agiven composition after other ingredients are determined. Although anypharmaceutically acceptable surfactant, stabilizer, preservative,coloring agent, buffering agents, emulsifying agents, thickeners,solvents, or perfuming agents may be used, certain compounds or mixturesare preferred as discussed below.

[0049] Preferred surfactants, including both the foaming and non-foamingtype, including, but not limited to, sodium laureth sulfate, sodiumlaureth-13 carboxylate, disodium laureth sulfosuccinate, disodiumcocoamphodiacetate, and the like, and mixtures thereof. More preferably,at least one amphoteric surfactant is included in the composition, suchas disodium cocoamphodiacetate. The amphoteric surfactant, incombination with citric acid, inhibits hydrogen peroxide decomposition.The surfactant component may be present in an amount from about 10 to 90weight percent, preferably about 20 to 80, and more preferably about 30to 70 weight percent of the composition.

[0050] The term “inhibit hydrogen peroxide decomposition,” as usedherein, means to at least stop the rate of decomposition fromincreasing, preferably to inhibit the decomposition entirely, and morepreferably to substantially inhibit the decomposition altogether.“Substantially inhibit,” as used herein, means that less than about 10weight percent, preferably less than about 3 weight percent, and morepreferably less than about 1 weight percent, of the hydrogen peroxidedecomposes over a three month period of time.

[0051] A preferred stabilizer includes glycol stearate or PEG-150distearate. The stabilizer, when used, is typically present in an amountfrom about 0.1 to 5 weight percent of the composition.

[0052] Preferred preservatives include tetrasodium ethylene-diaminetetraacetic acid (EDTA), methylparaben, benzophenone-4,methylchloroisothiazolinone, methylisothiazolinone, and the like, andmixtures thereof. Preservatives, when used, are typically present in anamount from about 0.01 to 6 weight percent, preferably about 0.05 to 4weight percent, and more preferably from about 0.1 to 2 weight percent.

[0053] Preferred coloring agents include FD&C Green No. 3, Ext. D&CViolet No. 2, FD&C Yellow No. 5, FD&C Red No. 40, and the like, andmixtures thereof. The coloring agents, when used, are typically presentin an amount from about 0.001 to 0.1 weight percent, and preferably fromabout 0.005 to 0.05 weight percent of the composition.

[0054] Anti-oxidants of both the enzymatic and non-enzymatic type may beincluded in the compositions and methods of the invention. For example,superoxide dismutase (SOD), catalase, and glutathione peroxidase arenatural enzymatic anti-oxidants used by the body that may besupplemented with the compositions herein. Suitable non-enzymaticanti-oxidants include, but are not limited to, Vitamin E (e.g.,tocopherol), Vitamin C (ascorbic acid), carotenoids, Echinacoside andcaffeoyl derivatives, oligomeric proanthocyanidins or proanthanols(e.g., grape seed extract), silymarin (e.g., milk thistle extract,Silybum marianum), ginkgo biloba, green tea polyphenols, and mixturesthereof. Carotenoids are powerful antioxidants, and they includebeta-carotene, canthaxanthin, zeaxanthin, lycopen, lutein, crocetin,capsanthin, and the like. Indeed, any pharmaceutically acceptablecompounds suitable for administration orally or topically may be used asan anti-oxidant in the compositions. Preferably, the anti-oxidantcomponent includes Vitamin E, Vitamin C, or a carotenoid. Theanti-oxidant component, when used, is present in an amount sufficient toinhibit or reduce the effects of free-radicals. The anti-oxidantcomponent may be present in an amount from about 0.001 to 1 weightpercent, preferably from about 0.01 to 0.5 weight percent of thecomposition.

[0055] The pharmaceutical compositions of the invention may also includeone or more of a local analgesic or anesthetic, antiyeast agent,antiperspirant, antipsoriatic agents antiaging agents, antiwrinklesagent, sun screen and sun blocking agents, skin lightening agents,depigmenting agents, vitamins, hormones and retinoids. Particularlypreferred are compositions further comprising a local analgesic oranesthetic to alleviate the pain and discomfort associated withinflammatory skin diseases. Local anesthetic include, but are notlimited to, lidocaine.

[0056] The pharmaceutical compositions of the invention may furtherinclude one or more of an immuno-enhancer to stimulate the bodies immunesystem. A suitable immuno-enhancer useful in the compositions of theinvention is Aldara (Immiquimod). The immuno-enhancer may be present inan amount from about 0.1 to 10 weight percent, preferably from about 0.5to 5 weight percent of the composition.

[0057] The ranges of the components of the pharmaceutical compositionmay vary, but the active ingredients should be understood to add to 100weight percent of the active pharmaceutical composition. Thecompositions may be prepared in high concentrations for administrationto be removed shortly thereafter, as well as in lower concentrationsthat are safer for products that can remain in contact with the skin forlonger times.

[0058] The present invention is further directed to a method ofpreventing, treating, or managing one or more inflammatory skinconditions. The methods of the invention comprise administering to apatient in need thereof a therapeutically effective amount of thecompositions of the invention.

[0059] The term “therapeutically effective amount,” as used herein,means that amount of the pharmaceutical composition that provides atherapeutic benefit in the treatment, prevention, or management of oneor more skin conditions.

[0060] The magnitude of a prophylactic or therapeutic dose of thecomposition in the acute or chronic management of inflammatory skinconditions will vary with the severity of the condition to be treated.The dose, and perhaps the dose frequency, will also vary according tothe age, body weight, and response of the individual patient. Ingeneral, a preferred topical daily dose range, in single or divideddoses, for the conditions described herein should be from about 1 mg to20,000 mg, more preferably about 2,000 mg to 16,000 mg, and mostpreferably about 6,000 mg to 10,000 mg of the active components (i.e.,excluding excipients and carriers).

[0061] Those of ordinary skill in the art will also understand thattopical effectiveness of pharmaceuticals requires percutaneousabsorption and bioavailability to the target site. Thus, thecompositions and methods of the invention require penetration throughthe stratum corneum into the epidermal layers, as well as sufficientdistribution to the sites targeted for pharmacologic action. Withoutwishing to be bound by theory it is believed that the presences of thehydrogen peroxide and the moisturizing agent facilitate penetration ofthe anti-inflammatory through the stratum corneum into the epidermallayers.

[0062] It is further recommended that children, patients aged over 65years, and those with impaired renal or hepatic function initiallyreceive low doses, and that they then be titrated based on individualresponse(s) or blood level(s). It may be necessary to use dosagesoutside these ranges in some cases, as will be apparent to those ofordinary skill in the art. Further, it is noted that the clinician ortreating physician will know how and when to interrupt, adjust, orterminate therapy in conjunction with individual patient response.

[0063] The pharmaceutical compositions used in the methods of thepresent invention include the active ingredients described above, andmay also contain pharmaceutically acceptable carriers, excipients andthe like, and optionally, other therapeutic ingredients.

[0064] Suitable dosage forms for topical administration include, but arenot limited to, dispersions, lotions; creams; gels; pastes; powders;aerosol sprays; syrups or ointments on sponges or cotton applicators;and solutions or suspensions in an aqueous liquid, non-aqueous liquid,oil-in-water emulsion, or water-in-oil liquid emulsion. Because of itsease of administration, a cream, lotion, or ointment represents the mostadvantageous topical dosage unit form, in which case liquidpharmaceutical carriers may be employed in the composition. Thesecreams, lotions, or ointments, may be prepared as rinse-off or leave-onproducts, as well as two stage treatment products for use with otherskin cleansing or managing compositions. In a preferred embodiment, thecompositions are administered as a rinse-off product in a higherconcentration form, such as a gel, and then a leave-on product in alower concentration to avoid irritation of the skin. Each of these formsis well understood by those of ordinary skill in the art, such thatdosages may be easily prepared to incorporate the pharmaceuticalcomposition of the invention.

[0065] The compositions of the invention may be prepared by any of themethods of pharmacy, but all methods include the step of bringing intoassociation the carrier(s) with the active ingredient, which constitutesone or more necessary ingredients. In general, the compositions areprepared by uniformly and intimately admixing the active ingredient withliquid carriers or finely divided solid carriers or both, and then, ifnecessary, shaping the product into the desired presentation.

[0066] Desirably, each unit dose, e.g., gel, cream, or ointment,contains from about 1 mg to 2,000 mg of the active ingredients,preferably about 200 mg to 1,600 mg, and more preferably about 600 mg to1,000 mg of the composition.

[0067] The methods of the invention may further comprise administeringone or more additional dermatological agents by a route ofadministration other than topically. Any suitable route ofadministration may be employed for providing the patient with aneffective dosage of the additional component including, but not limitedto, oral, intraoral, rectal, parenteral, topical, epicutaneous,transdermal, subcutaneous, intramuscular, intranasal, sublingual,buccal, intradural, intraocular, intrarespiratory, or nasal inhalationand like forms of administration. Preferably, the additional componentis administered orally.

[0068] Preferably, the additional component is a moisturizer oranti-inflammatory agents. Preferred moisturizers for oral administrationinclude, but are not limited to, panthenol; primrose oil; GLA 3 andother fish oils that may include, for example, the omega-3 and omega-6oils and/or linoleic acid; and flax seed oil. Preferredanti-inflammatory agents for oral administration include, but are notlimited to, aspirin, ibuprofen, ketoprofen, and naproxen. In anotherembodiment the additional component is an analgesic or anesthetic.

EXAMPLES

[0069] The invention is further defined by reference to the followingexamples describing in detail the preparation of the compound and thecompositions used in the methods of the present invention, as well astheir utility. The examples are representative, and they should not beconstrued to limit the scope of the invention.

Example 1 Skin Cleanser Formulation

[0070] A pharmaceutical composition according to the invention may beprepared for cleansing skin as set forth below: Ingredient TradeName/Supplier % by Weight Part A Deionized Water N/A 49.2 TrisodiumEthylene-Diamine- HAMP-ENE Na₃T/Akzo Nobel 0.2 Tetraacetic Acid (EDTA)Sodium Laureth-13 SURFINE WLL/Finetex 10 Carboxylate Disodium LaurethMACKANATE EL/McIntyre 17 Sulfosuccinate Group DisodiumCocoamphodiacetate MONATERIC CDX-38/Mona 11 PEG-150 PentaerythritylCROTHIX/Croda 1.5 Tetrastearate PEG-150 Distearate KESSCO PEG 6000DS/Stepan .7 Methylparaben N/A 0.2 Part B Salicylic Acid Salicylic Acid,powder, 1.6 USP/Spectrum Citric Acid N/A 1.5 Triclosan IRGASANDP300/Ciba 0.3 Part C PPG-26-Buteth-26, PEG-40 SOLUBILISANT LR1/Les 2Hydrogenated Castor Oil Colorant Wackherr SA Fragrance (Parfum)Fragrance —BELL #J7393/Bell 0.3 Flavors and Fragrances Menthol MentholCrystals, USP 0.1 Part D Butylene Glycol, Deionized ACTIPHYTE OF BLACK0.1 water, Black Cohosh SNAKEROOT BG50/Active (Cimicifuga Racemosa)Extract Organics Butylene Glycol, Deionized ACTIPHYTE OF JAPANESE 0.1water, Camellia Oleifera GREEN TEA BG50/Active Extract Organics SodiumPeroxylinecarbolic AJIDEW-50/Ajinomoto 0.2 Acid (PCA) CocamidopropylPG-Dimonium PHOSPHOLIPID PTC/Mona 1 Chloride Phosphate Part E HydrogenPeroxide Hydrogen Peroxide, 35% 3 solution, technical 100% #CROTHIX iscommercially available from Croda Inc. of Parsippany, NJ; KESSCO PEG 600DS is commercially available from Stepan Co. of Northfield, IL;IRGASANDP300 is commercially available from Ciba Specialty ChemicalsCorp. of Albemarle, NC; SOLUBILISANT LR1 is commercially available fromLes Colorant Wackherr SA of St. Ouen L'Aumone, France; #BELL #J7393 iscommercially available from Bell Flavors and Fragrances of Northbrook,IL; ACTIPHYTE OF BLACK SNAKEROOT BG50 and ACTIPHYTE OF JAPANESE GREENTEA BG50 are commercially available from Active Organics of Dallas, TX;and AJIDEW-50 is commercially available from Ajinomoto U.S.A. Inc. ofTeaneck, NJ.

[0071] Deionized water was metered into the processing tank and mixingsubsequently begun. The water was heated to 75° C. and the remainder ofPart A was added and mixed until uniform. The mixture was cooled to 60°C. and the Part B ingredients were added and mixed until uniform. Themixture was then cooled to 50° C. In a separate vessel, Part C waspremixed until uniform and then added to the mixture of Parts A and B.Parts A, B, and C were mixed until uniform and cooled to 40° C. The PartD ingredients were added and mixed until uniform, then cooled to 30° C.Part E was added and mixed until uniform, resulting in a colorless,clear, slightly viscous fluid having a pH at 25° C. of between 4 to 4.5and a viscosity between 3,000 to 4,000 cps (RVT: #4 @ 10 rpm @ 25° C.).

Example 2 Advanced Acne Prone Skin Formulation

[0072] A pharmaceutical composition according to the invention may beprepared for treating skin prone to acne as set forth below: IngredientTrade Name/Supplier % by Weight Part A Deionized Water N/A 46.7Hydroxyethylcellulose CELLOSIZE 1 QP52,000H/Amerchol Part B TetrasodiumEthylene-Diamine- HAMP-ENE 220/Akzo Nobel 0.1 Tetraacetic Acid (EDTA)Butylene Glycol 1,3-butylene glycol/Ashland 5 Aloe Barbadensis Gel AloeVera Freeze Dried 0.1 Powder 200:1/Aloe Methyl Gluceth-10 GLUCAME-10/Amerchol 3 Witch Hazel (Hamamelis Witch Hazel Distillate, 14% 3Virginiana) Distillate Zinc Acetate Zinc Acetate, crystals, 0.5 USP/FCCOrange (Citrus Aurantium NATURAL ORANGE 0.3 Dulcis) ExtractMethylparabenEXTRACT #71689/ Flavurence Dipotassium Glycyrrhizate N/A 0.3 Lecithin,Tocopherol and OXYSOMES/Barnett 0.3 Magnesium Ascorbyl PhosphatePalmitoyl GLYCOSPHERE PCO/Kobo 0.2 HydroxypropyltrimoniumAmylopectin/Glycerin Crosspolymer, Lecithin, Grape (Vitis Vinifera) SeedExtract Palmitoyl GLYCOSPHERE GT/Kobo 0.5 HydroxypropyltrimoniumAmylopectin/Glycerin Crosspolymer, Lecithin, Camellia Sinensis ExtractEpilobium Angustifolium Canadian Willowherb Whole 0.5 Extract Extract(5% in water)/Fytokem Butylene Glycol and Water and ACTIPHYTE OF ARNICA0.5 Arnica Montana Extract BG50/Active Organics Part C Alcohol(denatured) SD Alcohol 40-B, Anhydrous/ 20 Salicylic Acid SalicylicAcid, powder, 1 USP/FCC/Spectrum Triclosan IRGASAN DP300/Ciba 0.4 Part DPPG-5-Ceteth-20 PROCETYL AWS/Croda 1 PEG-40 Hydrogenated CastorCREMOPHOR RH-40/BASF 0.6 Oil Retinol and Polysorbate 20 RETINOL 50C/BASF0.1 Phytonadione N/A 0.1 Linoleic Acid EMERSOL 315/Henkel 0.3 Part EGlycolic Acid GLYPURE = 70% Glycolic 9 Acid/DuPont Part F Deionizedwater N/A 2 Sodium Hydroxide Sodium Hydroxide, pellets, 2 USP/NF Part GHydrogen Peroxide Hydrogen Peroxide, 35% 1.5 solution, technical 100%#is commercially available from Barnet Products Corporation of EnglewoodCliffs, NJ; Canadian Willowherb Whole Extract (5% in water) iscommercially available from Fytokem, Inc. of Saskatoon, SK CANADA;GLYCOSPHERE PCO and GLYCOSPHERE GT are commercially available from #KoboProducts Inc. of South Plainfield, NJ; ACTIPHYTE OF ARNICA BG50 iscommercially available from Active Organics of Dallas, TX; PROCETYL AWSis commercially available from Croda Inc. of Parsippany, NJ; CREMOPHORRH-40 and RETINOL 50C are commercially available from #BASF Corporationof Budd Lake, NJ; GLYPURE = 70% Glycolic Acid is commercially availablefrom DuPont of Wilmington, DE; EMERSOL 315 is commercially availablefrom Henkel Corp. of Hoboken, NJ.

[0073] Deionized water was metered into the processing tank and mixingsubsequently begun. CELLOSIZE QP52,000H was sprinkled in, heated to 70°C., and mixed until clear and uniform. The mixture was cooled to 40° C.Part B ingredients were added in the order above, with sufficient mixingafter each ingredient was added. The mixture was cooled to 25° C. andpremixed Part C ingredients were added and mixed until uniform. In aseparate tank, Part D was heated to 40° C. until the solids weredissolved and then added to the batch of Parts A, B, and C. The mixturewas mixed until uniform, then Part E was added and mixed until uniform.Premixed Part F was slowly added in increments as needed to obtain thedesired pH of 3.3 to 3.8 at 25° C., then Part G was added and mixeduntil completely uniform. This resulted in a straw-colored, clear toslightly hazy, slightly visqous liquid having a pH @ 25° C. of 3.3 to3.8 and a viscosity between 400 to 800 cps (RVT:#2 @ 10 rpm @ 25° C.).

Example 3 Skin Perfecting Lotion

[0074] A pharmaceutical composition according to the invention may beprepared for treating skin as set forth below: Ingredient TradeName/Supplier % by weight Part A Water (Aqua) Deionized water 60.6Carbomer CARBOPOL ULTREZ 10/ 0.3 B. F. Goodrich Sclerotium GumAMIGEL/Tri-K 0.6 Glycerin Glycerin 99.5%/Ashland 6.0 Butylene Glycol1,3-butylene glycol/Ashland 6.0 Allantoin Allantoin/ISP 0.6 PanthenolDEXPANTHENOL/Roche 0.6 Tetrasodium EDTA HAMP-ENE 220/Akzo 0.2Methylparaben Methylparaben/Ueno 0.3 Sodium PCA AJIDEW-50/Ajinomoto 0.5Part B Dicapryl Maleate BERNEL ESTER DCM/Bernel 6.0 SqualenePHYTOLANE/Barnet 0.8 Sorbitan Stearate ARLACEL 60/ICI 1.5 Stearic AcidEMERSOL 132/Henkel 1.3 Dimethicone DOW CORNING 200, 350cs./ 0.8 DowCorning C12-C15 Alkyl Benzoate FINSOLV TN/Finetex 3.0 Cetearyl Alcoholand Ceteareth HEXOTOL D/Heterene 0.6 Propylparaben Propylparaben/Ueno0.2 Part C Water (Aqua) Deionized water 0.3 TriethanolamineTriethanolamine 99%/Ashland 0.3 Part D Orange (Citrus Aurantium NATURALORANGE 0.3 Dulcis) Extract EXTRACT #71689/Flavurence Diazolidinyl UreaGERMALL II/ISP 0.3 Glycolipids and Hyaluronic Acid PHYTO/CER HA/Tri-K0.3 Palmitoyl GLYCOSPHERES PCO/Kobo 0.3 HydroxypropyltrimoniumAmylopectin/Glycerin Crosspolymer and Lecithin and grape (VitisVinifera) Seed Extract Palmitoyl GLYCOSPHERES GT/Kobo 0.3Hydroxypropyltrimonium Amylopectin/Glycerin Crosspolymer and Lecithinand Camellia Sinensis Extract Propylene Glycol Propylene Glycol/Ashland0.6 Algae Extract HAWAIIAN SEAPLANT 0.2 EXTRACT-J/Tri-K Lecithin andTocopherol and OXYSOMES/Barnet 0.6 Magnesium Ascorbyl Phosphate ButyleneGlycol and Honey ACTIPLEX 1072/Active 1.1 Extract (Mel) and MeadowsweetOrganics (Spiraea Ulmaria) Extract Talc and C9-C13 Fluoroalcohol PF-5TALC JA-46R/Kobo 0.8 and Phosphoric Acid Hydrolyzed Soy FlourRAFFERMINE/R.I.T.A. 0.3 Oat (Avena Sativa) Protein REDUCTINE/R.I.T.A.0.3 Phytonadione Phytonadione/Roche 0.01 Retinol and Polysorbate 20RETINOL 50C/BASF 0.1 Epilobium Angustifolium Extract Canadian WillowherbWhole 0.5 Extract (5% in water)/Fytokem Arnica Montana Extract ACTIPHYTEOF ARNICA 0.5 BG50/Active Organics Part E Hydrogen Peroxide HydrogenPeroxide, 35% 3 solution, technical 100.0 #DEXPANTHENOL and Phytonadioneare available from Roche Holdings, Inc. of Wilmington, DE; Methylparabenand Propylparaben are commercially available from Ueno Fine ChemicalsInc. of New York, NY AJIDEW N-50 is commercially available fromAjinomoto U.S.A. Inc. of Teaneck, NJ; #BERNEL ESTER is commerciallyavailable from Bernel Chemical Co. of Englewood, NJ; PHYTOLANE iscommercially available from Barnet Products Corporation of EnglewoodCliffs, NJ; ARLACEL 60 is commercially available from ICI Americas Inc.of Wilmington, DE; EMERSOL 132 #is commercially available from HenkelCorp. of Hoboken, NJ; DOW CORNING 200, 350 cs. is commercially availablefrom Dow Corning Corp. of Auburn, MI; FINSOLV TN is commerciallyavailable from Finetex Inc. of Elmwood Park, NJ; HETOXOL D iscommercially available from #Heterene Chemical Co. of Paterson, NJ;NATURAL ORANGE EXTRACT #71689 is commercially available from FlavurenceCorp. of Annandale, NJ; ACTIPLEX 1072 is commercially available fromActive Organics Inc. of Lewisville, TX; PF-5 TALC JA-46R is commerciallyavailable #from Kobo Products Inc. of South Plainfield, NJ; RAFFERMINEand REDUCTINE are commercially available from RITA Chemical Corp of EastNorthport, NY.

[0075] The Skin Perfecting Lotion was prepared by metering deionizedwater into a processing tank and mixing at high speed. CARBOPOL ULTREZ10 was sprinkled in. When the CARBOPOL ULTREZ 10 was completelydispersed, AMIGEL was added and the mixture mixed until smooth anduniform. The mixture was heated to 80° C., the remaining Part Aingredients were added, and then mixed until uniform. In a separatetank, the Part B ingredients were combined and heated to 80° C. untilall the solids were completely dissolved. Part B was added to Part A andthe resulting batch was mixed until uniform. Premixed Part C was addedand the batch mixed until homogeneous. The batch was cooled to 40° C.and the Part D ingredients were added and mixing continued until thetemperature of the mixture was 35° C. The resulting Skin PerfectingLotion was a light beige, opaque, viscous lotion having a pH at 25° C.of 6.2 to 7.2 and a viscosity of 14,000 to 24,000 cps. (RVT: #5 @10 rpm@ 25° C.).

Example 4 Acne Management Formula

[0076] A pharmaceutical composition according to the invention may beprepared for managing acne as set forth below: Ingredients TradeName/Supplier % by weight Part A Water (Aqua) Deionized Water 55.3Sclerotium Gum AMIGEL/Alban Muller 0.4 Disodium EDTA HAM-ENE NA₂/Akzo0.3 Allantoin Allantoin/ISP 0.2 Methylparaben Methylparaben/Ueno 0.3Zinc Oxide 66 ZINC OXIDE 0.3 U.S.P./Whitaker, Clark & Daniels Part BWater (Aqua) Deionized Water 10 Hydrolyzed Oat Flour and Oat RITAVENA5/R.I.T.A. 2.8 Betaglucan Dicaprylyl maleate BERNEL ESTER DCM/Bernel 3Glycerayl Stearate and PEG- ARLACEL 165/ICI 3 100 Stearate CetearylAlcohol and HEXOTOL D/Heterene 3 Ceteareth-20 PropylparabenPropylparaben/Ueno 0.1 Part D Salicylic Acid Salicylic Acid, powder,U.S.P.- 1.3 N.F./Spectrum Sulfur Sulfur, precipitated, U.S.P.- 6.5N.F./Spectrum Part E Water (Aqua) Deionized Water 3 Sodium HydroxideSodium Hydroxide, pellets, 0.1 U.S.P.-N.F./Spectrum Glycolic AcidGLYPURE 70% GLYCOLIC 6.5 ACID/DuPont Part F Orange (Citrus AurantiumORANGE EXTRACT 1.1 Dulcis) Extract PRODUCT #61522/Sunkist DiazolidinylUrea GERMALL II/ISP 0.4 Dipotassium Glycyrrhizate Dipotassium 0.3Glycyrrhizinate/Int'l Sourcing Lecithin and Tocopherol andOXYZOMES/Barnett 0.3 Magnesium Ascorbyl Phosphate Palmitoyl GLYCOSPHERESPCO/Kobo 0.3 Hydroxypropyltrimonium Amylopectin/Glycerin Crosspolymerand Lecithin and Grape (Vitis Vinifera) Seed Extract Part G HydrogenPeroxide Hydrogen Peroxide, 35% 1.5 solution, technical 100.0 #iscommercially available from Whitaker, Clark & Daniels of SouthPlainfield, NJ; Salicylic Acid, powder, U.S.P.-N.F., Sulfur,precipitated, U.S.P.-N.F. and Sodium Hydroxide, pellets, U.S.P.-N.F. arecommercially available from Spectrum Mfg. Corp of New Brunswick, NJ;ORANGE EXTRACT #PRODUCT #61522 is commercially available from SunkistGrowers, Inc. of Van Nuys, CA; Dipotassium Glycyrrhizinate iscommercially available from International Sourcing Inc. of Upper SaddleRiver, NJ.

[0077] The Acne Management Formula was prepared by metering deionizedwater into a processing tank and mixing at high speed. AMIGEL wassprinkled in. When the AMIGEL was completely dispersed, the mixture washeated to 85° C. and the remaining Part A ingredients were added and themixture mixed well after each addition. In a separate tank, Part B washeated to 100° C., mixed until smooth, cooled to 80° C. and added to thebatch. The resulting batch was mixed well. In another tank, the Part Cingredients were heated to 75° C. When all the solids dissolved, Part Cwas added to the batch, the batch was mixed until smooth and uniform,and the batch cooled to 50° C. Part D ingredients were added to thebatch, the batch was homogenized for 5 to 10 minutes until the batch wassmooth and uniform, and the batch was cooled to 40° C. The deionizedwater of part E was premixed with the sodium hydroxide pellets and theresulting solution was mixed well until all solids were dissolved. Whilemixing the solution, glycolic acid was slowly added in increments andthe solution was mixed until homogeneous. The solution was added to thebatch and the Part F ingredients were added to the batch. The batch wasmixed and cooled to 35° C. The Acne Management Formula was a lightyellow, opaque smooth lotion having a pH at 25° C. of 3.8 to 4.8 and aviscosity of 10,000 to 20,000 cps. (RVT: #5 @10 rpm @ 25° C.).

Example 5 Clarifying Skin Cleanser

[0078] A pharmaceutical composition according to the invention may beprepared for managing acne as set forth below: Ingredients TradeName/Supplier % by weight Part A Water (Aqua) Deionized Water 48.5Sodium Lauroyl Oat Amino PROTEOL O.A.T./Seppic 2 Acid Decyl GlucosideORAMIX NS-10/Seppic 3 Cocamidopropyl Betaine AMPHOSOL CA/Stephan 12.5Disodium Laureth MACKANATE EL/McIntyre 24 Sulfosuccinate PEG-120 MethylGlucose GLUCAMATE DOE- 3.5 Dioleate 120/Amerchol MethylparabenMethylparaben/Ueno 0.2 PEG-150 Pentaerythrityl CROTHIX/Croda 0.25Tetrastearate Part B Salicylic Acid Salicylic Acid, powder, 2USP/Spectrum Tetrasodium EDTA HAMP-ENE-100/Akzo 0.3 Triclosan IRGASAND300/Ciba Specialty 0.2 Chemicals Part C PPG-26-Buteth-26 and PEGSOLUBILISANT LRI/ 2 40Hydrogenated castor Oil Whittaker, Clark & DanielsFragrance Fragrance-BELL #J7393/Bell 0.3 Menthol Menthol Crystals, USP/0.1 Spectrum Part D Butylene Glycol and water ACTIPHYTE OF BLACK 0.2(aqua) and Black Cohosh SNAKEROOT BG50/Active (Cimicifuga Racemosa)Extract Organics Butylene Glycol and water ACTIPHYTE OF JAPANESE 0.2(aqua) and Camellia Oleifera GREEN TEA BG50/Active Extract OrganicsSodium PCA AJIDEW N-50/Ajinomoto 0.4 Imidazolidinyl Urea GERMALL 115/ISP035 100.0 #available from Akzo Nobel Inc. of Dobbs Ferry, NY;SOLUBILISANT LRI is commercially available from Whitaker, Clark &Daniels of South Plainfield, NJ; GERMALL 115 is commercially availablefrom ISP Chemicals Inc. of Calvert City, KY.

[0079] The Clarifying Skin Cleanser was prepared by metering deionizedwater into a processing tank, mixing, and heating to 75° C. The part Aingredients were added and mixed until all the solids dissolved. Theresulting mixture was cooled to 60° C. In a separate vessel the Part Bingredients were combined. The Part B ingredients were then added toPart A and the resulting batch was mixed until uniform. The resultingmixture was cooled to 50° C. In a separate vessel the Part C ingredientswere mixed until uniform. The part C ingredients were added to the batchand the resulting batch was mixed until uniform. The batch was cooled to40° C. and the part D ingredients were added and mixing continued untiluniform followed by cooling to 30° C. The Clarifying Skin CleanserFormula was a pale yellow, slightly viscous liquid having a pH at 25° C.of 4.5 to 5.5 and a viscosity of 5,000 to 9,000 cps. (RVT: # @10 rpm @25° C.).

Example 6 Antimicrobial Effectiveness of the Invention—Advanced AcneProne Skin Formulation

[0080] Culture Preparation

[0081]Escherichia coli (ATCC # 8739), Staphylococcus pureus (ATCC #6533), Pseudomonas aeruginosa (ATCC # 9027) were each propagated inTrypicase Soy Broth (TSB) at 35° C. for 24 hrs. Candida albicans (ATCC #10231), and; Aspergillus niger (ATOC # 16404) were propagated in Yeastand Mold Broth (YM) at 24° C. for 72 h. One loop of each bacteriaculture was streaked onto Trypticase Soy Agar (TSA) and the yeast andmold onto Sabouraud Dextrose Agar (SDA). The bacterial and yeastcultures were incubated for 24 h at 35° C. and 48 h at 24° C.,respectively. The mold culture was incubated for 5 days at 24° C.Following appropriate incubation, the surface growth of the organismswere washed with sterile Saline TS. Additional saline was added toreduce the microbial count. Each respective cell suspension was furtherdiluted with sterile saline TS to an appropriate concentration.

[0082] Product Inoculation

[0083] Five 20-g portions of the Advanced Acne Prone Skin Formula ofExample 2 was aseptically placed into sterile bottles. Each bottle wasindependently inoculated with 0.1 mL of the inoculum suspension.

[0084] Target Inoculation Concentration

[0085] A final concentration of 10⁵ and 10⁶ cfu/g of product wasobtained. This spike suspension was assayed for each respective organismto determine the initial microbial load in the product. All enumerationanalyses were performed by preparing serial 10-fold dilutions inButterfield's Phosphate Buffered Diluent (BPBD), and then plated usingthe pour plate technique on respective media.

[0086] Test Intervals

[0087] An enumeration of the target organisms were performed on eachinoculum. Immediately after inoculation (less than 1 minute), eachproduct was assayed to determine the density of viable target organismsaccording to the pour plate technique. Each sample was tested againafter 2 and 4 minutes. A 1-g portion was removed and mixed with 9.9 mLof BPBD. Serial dilutions were prepared as appropriate. Test samplescontaining bacterial cultures were plated with TSA and incubated for 48h at 35° C. Samples containing yeast and mold were plated with SDA andincubated for 5 days at 24° C.

[0088] Results

[0089] The following results were obtained for each of the fiveorganisms.

[0090] Test Organism: Candida albicans (ATOC # 10231)

[0091] Theoretical Inoculum Level: 400,000 cfu/g Testing ScheduleRecovery Levels (cfu/g) (Time: minutes) Advanced Acne Prone Skin Formula0 (less than 1) <10 2 <10 4 <10

[0092] Test Organism: Aspergillus niger (ATCC # 16404)

[0093] Theoretical Inoculum Level: 160,000 cfu/g Testing ScheduleRecovery Levels (cfu/g) (Time: minutes) Advanced Acne Prone Skin Formula0 (less than 1) <10 2 <10 4 <10

[0094] Test Organism: Escherichia coli (ATCC # 8739)

[0095] Theoretical Inoculum Level: 1,000,000 cfu/g Testing ScheduleRecovery Levels (cfu/g) (Time: minutes) Advanced Acne Prone Skin Formula0 (less than 1) <10 2 <10 4 <10

[0096] Test Organism: Staphylococcus aureus (ATCC # 6538)

[0097] Theoretical Inoculum Level: 700,000 Testing Schedule RecoveryLevels (cfu/g) (Time: minutes) Advanced Acne Prone Skin Formula 0 (lessthan 1) <10 2 <10 4 <10

[0098] Test Organism: Pseudomonas aeruginosa (ATCC #9027)

[0099] Theoretical Inoculum Level: 260,000 Testing Schedule RecoveryLevels (cfu/g) (Time: minutes) Advanced Acne Prone Skin Formula 0 (lessthan 1) <10 2 <10 4 <10

[0100] Discussion and Conclusion

[0101] The Advanced Acne Prone Skin Formulation prepared according tothe present invention exhibited excellent antimicrobial properties. Inless than one minute there was greater than a 99.99% reduction in levelsof Candida albicans, Escherichia coli, Staphylococcus aureus,Pseudomonas aeruginosa, and Aspergillus niger.

Example 7 Antimicrobial Effectiveness of Another Formulation of theInvention—Clarifying Skin Cleanser

[0102] Culture Preparation

[0103]Escherichia coli (ATCC # 8739), Staphylococcus pureus (ATCC #6533), and Pseudomonas aeruginosa (ATCC # 9027) were propagated inTrypicase Soy Broth (TSB) at 35° C. for 24 h. Candida albicans (ATCC #10231) and Aspergillus niger (ATOC # 16404) were propagated in Yeast andMold Broth (YM) at 24° C. for 72 h. One loop of each bacteria culturewas streaked onto Trypticase Soy Agar (TSA) and the yeast and mold ontoSabouraud Dextrose Agar (SDA). The bacterial and yeast cultures wereincubated for 24 h at 35° C. and 48 h at 24° C., respectively. The moldculture was incubated for 5 days at 24° C. Following appropriateincubation, the surface growth of the organisms were washed with sterileSaline TS. Additional saline was added to reduce the microbial count.Each respective cell suspension was further diluted with sterile salineTS to an appropriate concentration.

[0104] Product Inoculation

[0105] Five 20-g portions of the Clarifying Skin Cleanser of Example 1was aseptically placed into sterile bottles. Each bottle wasindependently inoculated with 0.1 mL of the inoculum suspension.

[0106] Target Inoculation Concentration

[0107] A final concentration of 10⁵ and 10⁶ cfu/g of product wasobtained. This spike suspension was assayed for each respective organismto determine the initial microbial load in the product. All enumerationanalyses were performed by preparing serial 10-fold dilution's inButterfield's Phosphate Buffered Diluent (BPBD), and then plated usingthe pour plate technique on respective media.

[0108] Test Intervals

[0109] An enumeration of the target organisms were performed on eachinoculum. Immediately after inoculation (less than 1 minute), eachproduct was assayed to determine the density of viable target organismsaccording to the pour plate technique. Each sample was tested againafter 2 and 4 minutes. A 1-g portion was removed and mixed with 9.9 mLof BPBD. Serial dilutions were prepared as appropriate. Test samplescontaining bacterial cultures were plated with TSA and incubated for 48h at 35° C. Samples containing yeast and mold were plated with SDA andincubated for 5 days at 24° C.

[0110] Results

[0111] The following results were obtained for each of the fiveorganisms.

[0112] Test Organism: Candida albicans (ATOC # 10231)

[0113] Theoretical Inoculum Level: 400,000 cfu/g Testing ScheduleRecovery Levels (cfu/g) (Time: minutes) Clarifying Skin Cleanser 0 (lessthan 1) 25,000 2 20,000 4 14,000

[0114] Test Organism: Aspergillus niger (ATCC # 16404)

[0115] Theoretical Inoculum Level: 160,000 cfu/g Testing ScheduleRecovery Levels (cfu/g) (Time: minutes) Clarifying Skin Cleanser 0 (lessthan 1) 1,400 2 1,200 4 1,000

[0116] Test Organism: Escherichia coli (ATCC # 8739)

[0117] Theoretical Inoculum Level: 1,000,000 cfu/g Testing ScheduleRecovery Levels (cfu/g) (Time: minutes) Clarifying Skin Cleanser 0 (lessthan 1) <10 2 <10 4 <10

[0118] Test Organism: Staphylococcus aureus (ATCC # 6538)

[0119] Theoretical Inoculum Level: 700,000 Testing Schedule RecoveryLevels (cfu/g) (Time: minutes) Clarifying Skin Cleanser 0 (less than 1)<10 2 <10 4 <10

[0120] Test Organism: Pseudomonas aeruginosa (ATCC #9027)

[0121] Theoretical Inoculum Level: 260,000 Testing Schedule RecoveryLevels (cfu/g) (Time: minutes) Clarifying Skin Cleanser 0 (less than 1)<10 2 <10 4 <10

[0122] Discussion and Conclusion

[0123] The Clarifying Skin Cleanser exhibited excellent antimicrobialproperties. In less than one minute there was a >99.99% reduction inlevels of Escherichia coli, Staphylococcus aureus, and Pseudomonasaeruginosa. In less than one minute, levels of Aspergillus niger andCandida albicans were reduced by 99.1% and 94.0%, respectively.

Example 8 Irritation Test Using the Invention

[0124] Irritation potential following epidermal contact by compositionsprepared according to the invention was examined. Fifty-three subjectsranging from 18 to 77 were evaluated. The patients were administered 0.2mL, or an amount sufficient to cover the upper back between thescapulae, of a 10 percent dilution of the formulation used in Example 2.The administration occurred by applying the composition to a 1″×¾″absorbent pad portion of an adhesive dressing, which was secured to thetreatment site on each patient. The test material remained in contactfor a total of 48 hours, and the test sites were evaluated at that timeand at 72 hours (24 hours later) for changes using a 6-point scaleranging from no visible skin reaction up to severe erythema, possibleedema, vesiculation, bullae and/or ulceration. One test subject did notcomplete the study. Observations indicated negative irritationthroughout the test interval, i.e. no visible skin reaction on a singlepatient.

Example 9 Hydrogen Peroxide Stability Test

[0125] The formulations prepared according to Examples 1 of theinvention having hydrogen peroxide, citric acid, salicylic acid, anantibacterial agent, and an amphoteric surfactant were heated to between40° C. to 45° C. for three months in an oven test. The oxygen content ofthe formula which was assayed after the stability test, showed no morethan 3 weight percent loss of the original hydrogen peroxide content.Such high stability provides an improved composition having a longshelf-life without substantial loss of efficacy.

Examples 10-12 Acne Treatment Regimen

[0126] An acne treatment regimen comprising Clarifying Cleanser,Advanced Acne Prone Skin Formula, Skin Perfecting Lotion and AcneManagement Formula (Examples 1, 2, 3, and 4, respectively) wasadministered to 15 subjects. Subjects were evaluated after 2 weeks and 4weeks use of the treatment regimen. Subjects were evaluated for totalfacial lesions, skin hydration and overall appearance of acne.

[0127] Testing of the Treatment Regimen

[0128] The acne treatment regimen comprising a ADVANCED ACNE PRONE SKINFORMULA, SKIN PERFECTING LOTION, ACNE MANAGEMENT FORMULA, and CLARIFYINGSKIN CLEANSER, prepared according to Examples 2, 3, 4, and 5,respectively, was administered to 15 subjects who exhibited a Grade 2-4acne condition according to the grading scale provided below:

[0129] 0: Facial skin need not be perfectly clear. A few scatteredcomedones or papules may be present, but these should be visible only onclose examination.

[0130] 2: About one fourth of facial area is involved, with smallpapules and large or small comedones. A few pustules or large prominentpapules may be present.

[0131] 4: About half of facial area is involved, with small papules andlarge or small comedones. A few pustules or large prominent papules areusually present. (If lesions are large, subject may have Grade 4severity, although less than half of facial area is involved).

[0132] 6: About three-fourths of facial area is involved, with papulesand/or large open comedones. (Lesser facial area of involvement ispermissible if inflammatory lesions are large) numerous pustules areusually present, some of which may be large.

[0133] 8: Practically all of facial area is involved, with lesions.Large prominent pustules are usually visible. Lesions are usually highlyinflammatory. Other types of acne (such as conglobata, including sinusand cystic types).

[0134] On the first day of the study all subjects were acclimated toambient temperature and relative humidity for fifteen minutes. After theequilibration period, a trained technician examined each subject's faceand recorded the number of inflammatory and non-inflammatory lesions ineach of six sections of the face. The lesions of the six sections weretotaled to obtain a global assessment score for each subject. Clinicalphotographs were taken in various poses for each subject and threeCorneometer measurements were taken.

[0135] Subjects were provided with the treatment regimen and were giventhe following instructions for the treatment regimen:

[0136] CLARIFYING CLEANSER: Apply twice per day (once in the morning andonce in the evening). Pour a small amount into hand or wash cloth. Applyto dampened face and neck. Massage gently into full lather. Rinsethoroughly with warm water and pat dry. Follow with ACNE PRONE SKINFORMULA.

[0137] ACNE PRONE SKIN FORMULA: Apply after cleansing twice per daily(once in the morning and once in the evening). Apply a small amount toface and neck or areas affected with acne. Follow with SKIN PERFECTINGLOTION.

[0138] SKIN PERFECTING LOTION: Use twice per day after cleansing andtreating skin. Apply a small amount to face and neck.

[0139] ACNE MANAGEMENT FORMULA: Use twice a day after using CLARIFYINGCLEANSER, ACNE PRONE SKIN FORMULA, and SKIN PERFECTING LOTION. Apply asmall amount to affected area to spot treat.

[0140] Subjects were required to maintain a daily diary indicating date,time of use and comments. Subjects were permitted to use their customarymake-up products during the study. However, subjects were instructed notto introduce any new cosmetic or facial treatment products during thestudy. Following the two week test material use period subjects wereevaluated for an interim count of total facial lesions, Corneometerreadings and clinical photographs. After four weeks of test material usesubjects returned with their diaries for a final lesion count,Corneometer readings and clinical photographs. Standard paired t-testswere used to determine statistically significant differences betweenbaseline and two (2) and four (4) week total facial lesion counts andCorneometer readings. Statistical significance exists for all p-valuesless than or equal to 0.05 at the 95% confidence level. Improvementscores for the appearance of acne in clinical photographs were analyzedusing Z-tests.

[0141] A total of fourteen subjects finished the study. One subject wasdisqualified immediately for lack of compliance with the InclusionCriteria of the protocol. A review of the daily diaries indicated thatfour (4) subjects reported redness, burning, stinging and/or“irritation” during the study period. One (1) of the subjects reportedthe onset of redness and burning on day five (5) of the studyimmediately after product application and lasting for fifteen (15) totwenty (20) minutes. The subject was instructed to discontinue testmaterial use on day ten (10) of the study. On day fourteen (14) thesubject was examined by a doctor and no evidence of skin irritation wasobserved. The subject was instructed to begin use of the treatmentmaterial at this time. The subject reported no evidence of irritationuntil day twenty four (24) of the study and completed studyparticipation. No evidence of irritation was observed at the finalvisit. The subjects reaction was diagnosed as dermatitis. The remainingsubjects reported symptoms following one (1) to two (2) uses of the testmaterial and completed study participation without further complaints.

Example 10 Total Lesion Count Following Treatment Regimen

[0142] The acne present on the skin of each subject was evaluated byvisual examination using the grading scale described herein. The numberof lesions on the face were counted at each visit. The number of openand closed comedones, as well as papules and pustules, were recorded. Aglobal assessment score, the total of all lesions, was recorded for eachvisit. Reductions in the global assessment score are indicative of areduced incidence and/or severity of acne lesions. The data for totallesion count is provided below. Total Lesion Count Baseline 2 Weeks 4Weeks Mean 44.4 33.4 27.6 Mean Percent Difference from Baseline −26%−40% σ   30%   22%

[0143] The regimen showed a statistically significant decrease oftwenty-six percent (26%) in the number of lesions observed after usingthe treatment regimen for two (2) weeks and a statistically significantdecrease of forty (40%) after using the treatment regimen for four (4)weeks compared to baseline (p=0.02 and p=1.07 E-05, respectively).

Example 11 Photographic Evaluation Following Treatment Regimen

[0144] Photographs of subjects were taken at designated visits using theCanfield Clinical System of imaging equipment. This particular systempermits comparison of photographs to be made with the confidence thatthe only factors which may have changed are those resulting fromtreatment. This is achieved by precisely and reproducibly positioningthe head of the subject and carefully controlling the lighting, filmtype and processing. Photographs were visually assessed and evaluated bya trained technician before and after use of the test material. Thefollowing scoring scale was used for visual assessment of the skin:

[0145] 1=no improvement

[0146] 2=slight improvement

[0147] 3=mild improvement

[0148] 4=moderate improvement

[0149] 5=extreme improvement

[0150] Improvement scores for the appearance of acne in clinicalphotographs were analyzed using Z-tests. For the two (2) and four (4)week scores, the number of subjects exhibiting improvements scoring atwo (2), three (3), four (4) or five (5) was compared to the number ofsubjects exhibiting no improvement, scored as a one (1). The improvementassessment of the overall appearance of acne, rated from clinicalphotographs, is provided below. Photographic Evaluation Score: 1 2 3 4 5Week 2 Number of Subjects 5 5 2 2 0 Assigned each Score Percentage 35.7%64.3% Z-Score −1.12 Week 4 Number of Subjects 4 4 5 1 0 Assigned eachScore Percentage 28.6% 71.4% Z-Score −1.77

[0151] The number of subjects exhibiting improvement from baseline inthe overall appearance of acne at two (2) weeks was greater thansubjects with no improvement. The Z-score obtained at two (2) weekscorresponds to improved skin appearance having a statisticalsignificance at a 74% confidence level. In the four (4) week photographthe number of subjects exhibiting improvement from baseline in theoverall appearance of acne was greater than subjects with noimprovement. The Z-score obtained at four (4) weeks corresponds toimproved skin appearance having statistical significance at a 92%confidence level.

Example 12 Moisturization via Corneometer Following Treatment Regimen

[0152] Changes in skin hydration were measured with a CORNEOMETER whichis a commercially available instrument (CM-820, Courage and KhazakaGermany) designed to measure changes in the capacitance of the skinresulting from small changes in the degree of hydration. The CORNEOMETERexpresses the capacitance of the skin in arbitrary unit of skinhydration (H). The instrument is capable of measuring the moisture ofthe stratum corneum to a depth of 0.1 mm and is used to measure theeffects of cosmetic preparations on the moisture content of the skin.Tests using the CORNEOMETER were conducted by taking 3 measurements, oneat the right and left cheek and one at the center of the skin, for eachsubject. The three measurements were then averaged for each subject. Thedata for skin hydration (H) is provided below. Skin Hydration (H)Baseline 2 Weeks 4 Weeks Mean 70.8 51.6 49.5 Mean Percent Differencefrom Baseline −26% −29% σ   14%   12%

[0153] The regimen showed a statistically significant decrease in SkinHydration, H, of twenty-six percent (26%) after using the treatmentregimen for two (2) weeks and a statistically significant decrease oftwenty-nine (29%) after using the treatment regimen four (4) weekscompared to baseline (p=2.27 E-05 and p=5.38 E-06, respectively). A lossin skin hydration is typically observed following treatment withanti-acne products.

Example 13 Skin Cleanser of Invention with Antifungal and AntibacterialAgents

[0154] A pharmaceutical composition according to the invention may beprepared for cleansing skin as set forth below: Ingredient TradeName/Supplier % by Weight Part A Deionized Water N/A 50 TrisodiumEthylene-Diamine- HAMP-ENE Na₃T/Akzo Nobel 0.2 Tetraacetic Acid (EDTA)Sodium Laureth-13 SURFINE WLL/Finetex 10 Carboxylate Disodium LaurethMACKANATE EL/McIntyre 17 Sulfosuccinate Group DisodiumCocoamphodiacetate MONATERIC CDX-38/Mona 11 PEG-150 PentaerythritylCROTHIX/Croda 1.5 Tetrastearate PEG-150 Distearate KESSCO PEG 6000DS/Stepan 0.7 Methylparaben N/A 0.2 Part B Clotrimazole N/A 0.8 CitricAcid N/A 1.5 Triclosan IRGASAN DP300/Ciba 0.3 Part C PPG-26-Buteth-26,PEG-40 SOLUBILISANT LR1/Les 2 Hydrogenated Castor Oil Colorant WackherrSA Fragrance (Parfum) Fragrance - BELL #J7393/Bell 0.3 Flavors andFragrances Menthol Menthol Crystals, USP 0.1 Part D Butylene Glycol,Deionized ACTIPHYTE OF BLACK 0.1 water, Black Cohosh SNAKEROOTBG50/Active (Cimicifuga Racemosa) Extract Organics Butylene Glycol,Deionized ACTIPHYTE OF JAPANESE 0.1 water, Camellia Oleifera GREEN TEABG50/Active Extract Organics Sodium PeroxylinecarbolicAJIDEW-50/Ajinomoto 0.2 Acid (PCA) Cocamidopropyl PG-DimoniumPHOSPHOLIPID PTC/Mona 1 Chloride Phosphate Part E Hydrogen PeroxideHydrogen Peroxide, 35% 3 solution, technical 100%

[0155] Deionized water was metered into the processing tank and mixingsubsequently begun. The water was heated to 75° C. and the remainder ofPart A was added and mixed until uniform. The mixture was cooled to 60°C. and the Part B ingredients were added and mixed until uniform. Themixture was then cooled to 50° C. In a separate vessel, Part C waspremixed until uniform and then added to the mixture of Parts A and B.Parts A, B, and C were mixed until uniform and cooled to 40° C. The PartD ingredients were added and mixed until uniform, then cooled to 30° C.Part E was added and mixed until uniform, resulting in a colorless,clear, slightly viscous fluid having a pH at 25° C. of between 4 to 6and a viscosity between 3,000 to 4,000 cps (RVT: #4 @ 10 rpm @ 25° C.).

Example 14 Skin Cleanser of Invention with Antifungal and AntibacterialAgents

[0156] A pharmaceutical composition according to the invention may beprepared for cleansing skin as set forth below: Ingredient TradeName/Supplier % by Weight Part A Deionized Water N/A 50 TrisodiumEthylene-Diamine- HAMP-ENE Na₃T/Akzo Nobel 0.2 Tetraacetic Acid (EDTA)Sodium Laureth-13 SURFINE WLL/Finetex 10 Carboxylate Disodium LaurethMACKANATE EL/McIntyre 17 Sulfosuccinate Group DisodiumCocoamphodiacetate MONATERIC CDX-38/Mona 11 PEG-150 PentaerythritylCROTHIX/Croda 1.5 Tetrastearate PEG-150 Distearate KESSCO PEG 6000DS/Stepan .7 Methylparaben N/A 0.2 Part B Ciclopirox Olamine N/A 0.8Citric Acid N/A 1.5 Triclosan IRGASAN DP300/Ciba 0.3 Part CPPG-26-Buteth-26, PEG-40 SOLUBILISANT LR1/Les 2 Hydrogenated Castor OilColorant Wackherr SA Fragrance (Parfum) Fragrance - BELL #J7393/Bell 0.3Flavors and Fragrances Menthol Menthol Crystals, USP 0.1 Part D ButyleneGlycol, Deionized ACTIPHYTE OF BLACK 0.1 water, Black Cohosh SNAKEROOTBG50/Active (Cimicifuga Racemosa) Extract Organics Butylene Glycol,Deionized ACTIPHYTE OF JAPANESE 0.1 water, Camellia Oleifera GREEN TEABG50/Active Extract Organics Sodium PeroxylinecarbolicAJIDEW-50/Ajinomoto 0.2 Acid (PCA) Cocamidopropyl PG-DimoniumPHOSPHOLIPID PTC/Mona 1 Chloride Phosphate Part E Hydrogen PeroxideHydrogen Peroxide, 35% 3 solution, technical 100%

[0157] Deionized water was metered into the processing tank and mixingsubsequently begun. The water was heated to 75° C. and the remainder ofPart A was added and mixed until uniform. The mixture was cooled to 60°C. and the Part B ingredients were added and mixed until uniform. Themixture was then cooled to 50° C. In a separate vessel, Part C waspremixed until uniform and then added to the mixture of Parts A and B.Parts A, B, and C were mixed until uniform and cooled to 40° C. The PartD ingredients were added and mixed until uniform, then cooled to 30° C.Part E was added and mixed until uniform, resulting in a colorless,clear, slightly viscous fluid having a pH at 25° C. of between 4 to 6and a viscosity between 3,000 to 4,000 cps (RVT: #4 @ 10 rpm @ 25° C.).

[0158] Various modifications of the invention in addition to those shownand described herein will be apparent to those skilled in the art fromthe foregoing description. Such modifications are also intended to fallwithin the scope of the appended claims. The foregoing disclosureincludes all the information deemed essential to enable those skilled inthe art to practice the claimed invention.

What is claimed is:
 1. A topical anti-inflammatory pharmaceuticalcomposition comprising: hydrogen peroxide in an amount sufficient tocleanse the skin; a moisturizing agent in an amount sufficient tofacilitates hydration of the skin; and an anti-inflammatory agent to inan amount sufficient to reduce inflammation of the skin.
 2. Thepharmaceutical composition of claim 1, wherein the hydrogen peroxide ispresent in an amount from about 0.01 to 6 weight percent by weight ofthe composition, the moisturizing agent is present in an amount of about0.01 to 20 weight percent by weight of the composition, and theanti-inflammatory agent is present in an amount of about 0.02 to 2weight percent by weight of the composition.
 3. The pharmaceuticalcomposition of claim 1, wherein the moisturizing agent is a hydrophobicmoisturizing agent.
 4. The composition of claim 3, wherein thehydrophobic moisturizing agent is ceramide, borage oil, tocopherol,tocopherol linoleate, dimethicone, glycerine, or a mixture thereof. 5.The pharmaceutical composition of claim 1, wherein the moisturizingagent is a hydrophilic moisturizing agent.
 6. The pharmaceuticalcomposition of claim 5, wherein the hydrophilic moisturizing agent ishyaluronic acid, sodium peroxylinecarbolic acid, wheat protein, hairkeratin amino acids, or a mixture thereof.
 7. The pharmaceuticalcomposition of claim 1, wherein the composition further comprises apharmaceutically acceptable carrier or excipient.
 8. A gel, paste,cream, lotion, emulsion, or ointment comprising the pharmaceuticalcomposition of claim
 1. 9. The pharmaceutical composition of claim 1,further comprising an exfoliant.
 10. The pharmaceutical composition ofclaim 9, wherein the exfoliant is an enzymatic exfoliant.
 11. Thepharmaceutical composition of claim 9, wherein the exfoliant is an mono-or -poly-hydroxy acid.
 12. The pharmaceutical composition of claim 11,wherein the exfoliant comprises an alpha-hydroxy acid, beta-hydroxyacid, or tannic acid.
 13. The pharmaceutical composition of claim 11,wherein the exfoliant comprises glycolic acid, lactic acid, citric acid,salicylic acid, or tannic acid.
 14. The pharmaceutical composition ofclaim 1, further comprising an amount of amphoteric surfactant and anamount of citric acid sufficient to inhibit hydrogen peroxidedecomposition for at least three months.
 15. The pharmaceuticalcomposition of claim 14, wherein the amount of amphoteric surfactant andcitric acid is sufficient to inhibit hydrogen peroxide decomposition at40° C. for at least three months.
 16. The pharmaceutical composition ofclaim 1, further comprising at least one of a surfactant, a stabilizer,a preservative, an anti-oxidant, or a coloring agent, which together maybe present in an amount from about 10.1 to 99.1 weight percent of thecomposition.
 17. A method of managing an inflammatory skin conditionwhich comprises topically administering to a patient a therapeuticallyeffective amount of: (1) hydrogen peroxide in an amount sufficient tocleanse the skin; (2) a moisturizing agent in an amount sufficient tofacilitates hydration of the skin; and (3) an anti-inflammatory agent toin an amount sufficient to reduce inflammation of the skin.
 18. Themethod of claim 17, wherein the skin condition treated is at least oneof dermatitis, psoriasis, folliculitis, rosacea, acne, impetigo,erysipelas, paronychia, erythrasma, and eczema.
 19. The method of claim17, wherein the amount of the hydrogen peroxide, moisturizing agent, andanti-inflammatory agent administered is about 1 mg to 20,000 mg per day.20. The method of claim 17, further comprising administering one or moresecond dermatological agents selected from a moisturizer,anti-inflammatory agent, analgesic, or anesthetic by a route other thantopical administration.
 21. The method of claim 20, wherein the one ormore second dermatological agents is a moisturizer selected frompanthenol, primrose oil, omega-3 fish oils, omega-6 fish oils, linoleicacid, flax seed oil, and mixtures thereof.
 22. The method of claim 20,wherein the one or more second dermatological agents is ananti-inflammatory agent selected from aspirin, ibuprofen, ketoprofen,naproxen, and mixtures thereof.
 23. The method of claim 17, furthercomprising administering one or more exfoliants in an amount sufficientto exfoliate at least a portion of the skin.
 24. The method of claim 23,wherein the exfoliant is an enzymatic exfoliant.
 25. The method of claim24, wherein the exfliant is an mono- or -poly-hydroxy acid.
 26. Themethod of claim 25, wherein the exfoliant comprises an alpha-hydroxyacid, beta-hydroxy acid, or tannic acid.
 27. The method of claim 26,wherein the exfoliant comprises glycolic acid, lactic acid, citric acid,salicylic acid, or tannic acid.